Continuous theta-burst stimulation of the prefrontal cortex in the macaque monkey: no evidence for within-target inhibition or cross-hemisphere disinhibition of neural activity

Continuous theta-burst stimulation (cTBS) can perturb neural activity and behavior by inducing effects that persist beyond the relatively short stimulation period. Although widely used in basic research and clinical settings, there lacks an understanding of the neurophysiological and behavioural effects of cTBS. Two assumptions motivating the use of cTBS are that it will i) inhibit neural activity in the targeted area, and ii) consequently disinhibit neural activity in the mirroring region in the contralateral cortex. Here, we test these assumptions in the oculomotor system of the rhesus macaque. In two macaques, we delivered cTBS between blocks of trials where they performed a delayed pro-/anti-saccade task, delivered cTBS to the right PFC (areas 8Ar and 46, which includes the frontal eye fields; 32 cTBS-PFC sessions), to the air as a SHAM control (27 cTBS-SHAM sessions), or to the nearby primary motor cortex as a brain control (21 cTBS-M1 sessions). Across these different types of sessions, we compared changes in oculomotor behavior (reaction times, error rates, peak saccade velocity), and changes in neural activity recorded from the left, contralateral PFC. Despite multiple lines of evidence consistent with TMS influencing neural activity in the cTBS-PFC and cTBS-M1 sessions, we found no behavioral evidence for inhibition of the right PFC in the cTBS-PFC sessions, nor any evidence for contralateral disinhibition in the left PFC. Our results call into question some of the fundamental assumptions underlying the application of cTBS.